The present invention relates to an improved method of producing 1-methoxycyclohepta-1,3,5-triene.
1-methoxycyclohepta-1,3,5-triene is a relatively non-toxic compound, gaseous at room temperature, which is used for the training of troops for defence purposes. As this gas has mild effects similar to those of "tear gas" on humans, troops may be trained, for example, in the proper use of gas masks in environments in which 1-methoxycyclohepta-1,3,5-triene has been introduced.
1-ethoxy-1,3,5-cycloheptatriene has been previously prepared in 37% yield by heating 7,7-dichloro-1-ethoxybicyclo[4.1.0]heptane in quinoline for about 10 minutes at 160.degree. C. -180.degree. C. (W. E. Parham et al., J.A.C.S., 84, 1755 (1962) and W. E. Parham et al., J.A.C.S., 87, 321 (1965)). The reaction is exothermic. Extending the heating time to 45 minutes resulted in a yield of only 5%. Similarly 1-methoxycyclohepta-1,3,5-triene has been made in 33% yield by heating 7,7-dibromo-1-methoxybicyclo[4.1.0]heptane in quinoline for 1 hour at 150.degree. C. (D. G. Lindsey and C. B. Reese, Tetrahedron, 21, 1673 (1965)).
Use of other aromatic bases instead of quinoline has been reported in the literature, but none of the desired product was reported. Refluxing 7,7-dichloro-1-ethoxybicyclo[4.1.0]heptane in pyridine for 75 minutes has produced 2-ethoxy-3-chloro-1,3-cycloheptadiene in 85% yield (W. E. Parham et al., J.A.C.S., 84, 1755 (1962) and W. E. Parham et al., J.A.C.S., 87, 321 (1965)). When 7,7-dibromo-1-methoxybicyclo[4.1.0]heptane is heated in 2,6-lutidine for 45 minutes at 135.degree. C., methoxybromocycloheptadienes were obtained in 70% yield (D. G. Lindsey and C. B. Reese, Tetrahedron, 21, 1673 (1965)).
Alternative methods of production of 1-methoxycyclohepta-1,3,5-triene have been reported. It has been made from cycloheptanone ketals by bromination and elimination (E. W. Garbisch, Jr., J. Org. Chem., 30, 2109 (1965)). 1-methoxycyclohepta-1,3,5-triene has also been made from tropylium tetrafluoroborate (W. R. Hydro, U.S. Pat. No. 4,249,025 (1981), G. A. Grant, Canadian Pat. No. 1,172,957 (1984)). It has been reported that the yield of this process is improved by adding a stabilizer, phenothiazine, to the reaction mixture (W.R. Hydro, U.S. Pat. No. 4,249,025 (1981)).
There are four possible isomers of 1-methoxycyclohepta-1,3,5-triene, but it has been shown that the isomers interconvert thermally (E. Weth and A. S. Dreiding, Proc. Chem. Soc., 59 (1964), and T. Nozoe and K. Takahashi, Bull. Chem. Soc. Jap., 38, 665 (1965)). The equilibrium mixture at 150.degree. C. consists of the 1-methoxy-,2-methoxy-, and 3-methoxy- isomers in the ratio 100:1:10 (E. Weth and A. S. Dreiding, Proc. Chem. Soc., 59 (1964)). None of the 7-methoxyisomer is found at equilibrium.
In experiments leading up to the present invention, it was attempted to produce 1-methoxycyclohepta-1,3,5-triene from 7,7-dichloro-1-methoxybicyclo[4.1.0]heptane. However, even after optimizing the reaction time and temperature, the reaction in quinoline gave only about 50% yield of 1-methoxycyclohepta-1,3,5-triene, with extensive tarry by-products. More seriously, the reaction could not be scaled-up safely. It was found that in large batches, exothermic reaction accompanied by exothermic decomposition of the product could cause the temperature to rise uncontrollably. For safe operation, the temperature should be kept below 150.degree. C., but the high boiling point of quinoline (238.degree. C.) allows the temperature to rise much higher.